Hs-chxcook



United States Patent 3,1816% SUBSTITUTED t-THEAZOLEDENQNES AND PROCESS THEREFGR Gerhard Satzinger, Memrningen, Allgau, Germany,

assignor to Warner-Hambert iharrnaceutical Company, Morris Plains, Ni, a corporation of Delaware No Drawing. Filed Mar. 6, 1961, Ser. No. $3,301 13 Claims. (Cl. 268-306.?)

The present invention relates to new and novel substituted 4-thiazolidinones of the formula:

wherein R is hydrogen, lower alkyl, aryl or in which n is 1 to 3 and R is di-lower alkylamino, aryl, or carbalkoxy in which the alkyl portion is lower a lryl; R is cyano 0 ALB,

in which R is di-lower alkylamino, lower alkoxy or aryl, or -SO R in which R is lower alkyl or aryl; and R is hydrogen or lower alkyl. The present invention also relates to a method of preparing these substituted 4-thiazolidinones.

The terms lower alkyl and lower alkoxy as used in the specification and in the claims refer to branched and straight chain aliphatic groups having 1 to 6 carbon atoms.

The substituted 4-thiazolidinones of this invention have been found to have interesting pharmacological activity as analgesics, sedatives, anti-inilammatory agents and choleretic agents. In use, they may be formulated with conventional pharmaceutical carriers to form such typical dosage units as tablets, capsules, solutions, suspensions, suppositories and the like. These new and novel compounds are also valuable intermediates useful in the production of additional new and novel 4-thiazolidinones and bis(4-thiazolidinones) which in turn have interesting pharmacological activity.

For example, compounds of the above formula wherein R is hydrogen, lower alkyl or aryl; R is cyano,

in which R is lower alkoxy or aryl, or 4O R in which R is lower alkyl or aryl; and R is hydrogen or lower allcyl, may be reacted in a basic medium with a compound of the formula R X wherein X is halogen and R is lower alkyl, lower alkenyl, lower alkynyl, the acyl radical of a lower alkyl carboxylic acid, aryl or (CI-l --R in which m is 1 to 3 and R is halogen, hydroxyl, aryl, the acyl radical or" a lower alkyl carboxylic acid, carballioxy in which the alkyl portion is lower allryl or /R N a in which R is lower alkyl or when taken with the amino nitrogen atom forms a piperidino, morpholino or pyrrolidino group to form compounds of the formula:

Patented June 1, 65

as described and claimed in my copending application Serial No. 93,318 filed Marchfi, 1961. The terms lower alkenyl and lower alkynyl as used hereinabove refer to branched or straight chain radicals having 2 to 6 carbon atoms and, respectively, a single double bond and a single triple bond.

In addition, the new and novel compounds of the present invention of the formula:

wherein R is hydrogen, lower alkyl or aryl, R is carbalkoxy in which the alkyl portion is lower alkyl and R is hydrogen or lower alkyl, may be converted to substituted bis(4-thiazolidinones) of the formula:

wherein A is an alkylene radical having 1 to 6 carbon atoms in which Y is halogen and B is an alkylene radical having 1 to 6 carbon atoms or a radical of the formula 2) a-lI 2) s These substituted bis(4-thiazolidinones), which also have interesting pharmacological activity, are described and claimed in US. Patent 3,072,671, issued January 8, 1963.

It has now been found that the new and novel substituted 4-thiazolidinones of this invention of the formula:

wherein R is hydrogen, lower alkyl, aryl or (CH ),,R in which n is 1 to 3 and R is di-lower alkylamino, aryl, or carbalkoxy in which the alkyl portion is lower alkyl; R; is cyano,

0 ll -CR5 in which R is di-lower alkylamino, lower alkoxy or aryl, or -S0 FR in which R is lower allcyl or ar-yl; and R is hydrogen or lower alkyl, may be prepared by the following reaction:

methylene-5-methyl-4-thiazolidinone, melting point 142- 143 C., colorless crystals from aqueous ethanol.

Analysis.Calc.: C, 46.73; H, 3.92; N, 18.17; S, 20.79. Found: C, 46.89; H, 3.83; N, 18.46; S, 20.38.

EXAMPLE 3 2-(N,N-dimethylcqrbamoylmethylene) -4-thia.zolidin0ne A mixture of 11.2 g. (0.1 mole) N,N-dimethylcyanoacetamide and 12 g. (0.1 mole) ethyl mercaptoacetate is condensed with potassium ethylate as described in Example 2. The reaction mixture is refluxed for /2 hour. Upon cooling, the potassium salt is precipitated, recovered and acidified as described in Example 2. Yield: 9 g.

is carried out in a basic anhydrous medium comprising an aliphatic alcohol having 1 to 6 carbon atoms, for example ethanol, methanol, tert.-butanol and the like, in the presence of an alkali metal, for example sodium or potassium, or an amine such as piperidine. The reaction may be carried out at a temperature between C. and the boiling point of the alcohol solvent used, with the reaction time normally being between about one-half hour and eight hours. Prior to the addition of the reactants to the reaction vessel, it is desirable that the vessel be freed of oxygen by flushing with an inert gas such as nitrogen.

The substituted 4-thiazolidinone separates as a pre-. cipitate of its alkali metal or amine salt which is then readily converted to the free acid by treatment with acid.

The following examples are included in order further to illustrate the present invention:

EXAMPLE 1 2-cyanomethylene-4-thiaz0lidinone A mixture of 6.6 g. (0.1 mole) malonitrile and 12 g. (0.1 mole) ethyl mercaptoacetate is quickly dropped into a solution of 2.3 g. (0.1 mole) sodium in 150 ml. absolute ethanol under stirring. The apparatus is initially flushed with nitrogen. The separation of the sodium salt begins under strong evolution of heat. After an additional hour the precipitate is sucked off, washed with some cold absolute ethanol, then with ether and air-dried. Yield: 16 g. (quantitative) of colorless crystals, very soluble in water, constituting the sodium salt of 2-cyanomethylene- 4-thiazolidinone. An aqueous solution of the sodium salt is strongly acidified. The precipitate is collected by filtration, Washed with water, ethanol and ether and air-dried. Yield 14 g. (quantitative) of colorless needles from water, aqueous ethanol or dimethylformamide/water 1:1, melting point 187 C. dec., constituting 2-cyanomethylene-4- thiazolidinone.

Analysis.Calcd.: C, 42.83; H, 2.88; N, 20.00; S, 22.85. Found: C, 42.93; H, 2.98; N, 20.44; S, 22.49.

EXAMPLE 2 Z-cyanomethylene-S-methyl-4-thiazolidinone (50%) of 2-(N,N-dimethylcarbamoylmethylene)-4-thiazolidinone, melting point 206208 C. dec., light yellow crystals from 70% ethanol.

Analysis.-Calc.: C, 45.15; H, 5.42; N, 15.04; S, 17.22. Found: C, 45.38; H, 5.49; N, 15.06; S, 17.00.

EXAMPLE 4 Z-Benzoylmethylene-4-thiaz0lidin0ne A mixture of 15 g. (0.1 mole) cyanoacetophenone and 12 g. (0.1 mole) ethyl mercaptoacetate is condensed with potassium ethylate as described in Example 2. The reaction mixture is refluxed for 3 hours. The mixture is cooled and the potassium salt is recovered and acidified A, as described in Example 2. Yield: 15 g. (70%) of 2- Found: C, 60.12; H, 4.18; N, 6.38; S, 14.23.

EXAMPLE 5 2-carbetIz0xymeZhylene-4-thiazolidinone A mixture of 11.3 g. (0.1 mole) ethyl cyanoacetate and 12 g. (0.1 mole) ethyl mercaptoacetate is condensed With sodium ethylate as described in Example 1. The reaction mixture is held at 60 C. for 1 hour and then cooled to room temperature, diluted with two volumes of water and acidified with I-ICl to pH 2. The precipitate is collected by filtration, washed with water and ethanol and dried. Yield: 18 g. (quantitative) of Z-carbethoxymethylene-4-thiazolidinone, melting point 145-147" C., colorless plates from aqueous ethanol.

Analysis-Cale: C, 44.90; H, 4.85; N, 7.48; S, 17.13. Found: C, 45.22; H, 5.13; N, 7.36; S, 17.18.

EXAMPLE 6 V Z-carbethoxymethylene-S-methyl-4-thiaz0lidin0ne A mixture of 12 g. (0.1 mole) ethyl cyanoacetate and 12 g. (0.1 mole) methyl a-mercaptopropionate is condensed with sodium ethylate as described in Example 1. The reaction mixture is refluxed for 2 hours and is then processed as described in Example 5. Yield: 20 'g. (quantitative) of 2-carbethoxymethylene-5-methyl-4-thiazolidinone, melting point 119 C., colorless crystals from Water.

Analysis.-Calc.: C, 47.74; H, 5.51; N, 6.96; S, 15.93.

' Found: C, 47.51; H, 5.53; N, 7.01; 'S, 15.71.

A mixture of 6.6 g. (0.1 mole) malodinitrile and 12 g.

(0.1 mole) methyl or-mercaptopro'pionate and 20 ml. absolute ethanol is quickly added to a solution of 4 g. (0.1

. mole) potassium in 130 ml. absolute ethanol with stirring.

The reaction 'proceeds under strong evolution of heat. Upon cooling to room temperature and standlng for 10 minutes, the precipitated potassium salt of 2-cyanomethy1- ene-5-methyl-4-thiazolidinone is recovered by filtration, washed with ethanol and ether, and dissolved in Water. The solution is acidified to pH 2 with HCl. The precipitate is collected by filtration, 'washed-with-water and-'eth--.

anol and dried. Yield: 15 .g. (quantitative) of 2-cyano;

' is added rapidly to a solution of 12 g. (0.1 mole) methyl- V EXAMPLE 7 2-[ (methylsdlfonyl methylene] -4-Ihiaz0lidin0ne A solution of 4 g. (0.1 mole) potassium and 12 g. (0.1 mole) ethyl mercaptoacetate in ml. absolute ethanol sulfonylacetonitrilein 150 ml. ethanol. The mixture is maintained for 1 hour at room temperature. The precipitated potassium salt is recovered and acidified as described in Example 2. Yield: 12 g. (63%) of 2-[(methyl sulfonyl)methylene]-4-thiazolidinone, melting point 163' 164 0., light yellow crystals from water. 5 a

s a Analysis-Cale; C, 31.07; H, 3.66; N, 7.25; S, 33.19. Found: C, 31.01; H, 3.84; N, 7.31; S, 32.66.

EXAMPLE 8 2-[ (phenylsulfonyl) methylene] -4-Ihiaz0lidin0ne A mixture of 18.1 g. 0.1 mole) phenylsulfonylacetonitrile and 12 g. 0.1 mole) ethyl mercaptoacetate is reacted at room temperature for 2 hours in the presence of potassium ethylate as described in Example 7. The precipitated potassium salt is recovered and acidified as described in Example 2. Yield: 20 g. (80%) of 2-[(phenylsulfonyl)rnethylene]-4-thiazolidinone, melting point 127 C., light yellow crystals from chloroform.

A2zalysis.-Calc.: C, 47.04; H, 3.56; N, 5.49; S, 25.12. Found: C, 46.99; H, 3.56; N, 5.55; S, 24.67.

EXAMPLE 9 2-[ (pl'zenylszzlfonyl methylene] -5-methyl-4-thiazolidincne A mixture of 18.1 g. (0.1 mole) phenylsulfouylacetonitrile and 12 g. (0.1 mole) methyl a-mercaptopropionate is reacted and the product recovered from the reaction mixture as described in Example 8 .to yield 2-[(phenylsulfonyDmethylene]-5-met.hyl 4 thiazolidinone, melting point 143145 C.

Analysis.--Calc.: C, 49.04; H, 4.12; N, 5.21; S, 23.81. Found: C, 49.16; H, 4.20; N, 5.18; S, 23.77.

EXAMPLE 10 2-(1 -carbethoxyetl'zylidene) -4 -th iazolidinone A mixture of 12.7 g. (0.1 mole) ethyl oc-cyanopropiomate and 12 g. (0.1 mole) ethyl mercaptoacetate is condensed with potassium ethylate as described in Example 2. The reaction mixture is refluxed for 1% hours and is then allowed to stand overnight at room temperature. The precipitated potassium salt is recovered and acidified as described in Example 2. Yield: 10 g. (50%) of 2- (1-carbethoxyethylidene)-4-thiazolidinone, melting point 161162 C., colorless crystals from methanol/dioxane 3:1.

Analysis.Calc.: C, 47.74; H, 5.51; N, 6.96; S, 15.93. Found: C, 48.08; H, 5.47; N, 7.02; S, 15.45.

EXAMPLE 11 2-(1-carbcflzoxyethylidene -5-meth il-4-thiazolidin one A mixture of 12.7 g. (0.1 mole) ethyl ot-CYZXHOPIOPiO- mate and 12 g. (0.1 mole) methyl a-mercapt-opropionate is reacted and the product recovered as described in Example 10 to yield 2-(l-carbethoxyethyiidene)-5-methyl- 4-thiazolidinone, melting point 149150 C.

Analysis.-Calc.: C, 50.20; H, 6.09; N, 6.51; S, 14.89. Found: C, 49.96; H, 5.99; N, 6.76; S, 14.64.

EXAMPLE 12 2 (1carbellzoxypropylidene) 4-tkiazolidinone A mixture of 14 g. (0.1 mole) ethyl :z-cyanobutyrate and 12 g. (0.1 mole) ethyl rnercaptoacetate is condensed with potassium ethylate as described in Example 2. The reaction mixture is maintained at 80 C. for 5 hours and thereafter the ethanol is distilled oil at reduced pressure. The residue is taken up in distilled water and acidified with HCl to pH 2. The precipitate is collected by filtration, Washed with ethanol and Water and dried. Yield: 11 g. (50%) of 2-(l-carbethoxypropylidene)-4thiazolidinone, melting point 155-15 6 C., colorless crystals from 50% aqueous ethanol.

Analysis-Cale: C, 50.21; H, 6.09; N, 6.51; 5, 14.90. Found: C, 50.51; H, 6.14; N, 6.58; S, 14.66.

EXAMPLE 13 2-(1 -carbethoxyprpyl idene) -mezhyl-4-thiazolidiiwne A mixture of 14 g. (0.1 mole) ethyl u-cyanobutyrate and 12 g. (0.1 mole) methyl u-mercaptopropionate is reacted and the product recovered as described in Example EXAMPLE 14 2-( I-carbezlzoxypentylidene -4-zhz'az0lidin0ne A mixture of 16.6 g. (0.1 mole) ethyl a-(n-butyl) cyano-acetate and 12 g. (0.1 mole) ethyl mercaptoacetate is condensed with potassium ethylate as described in Example 2. The reaction mixture is maintained at C. for 3 hours. After cooling to room temperature, the solution is diluted with an equal volume of distilled water and acidified with HCl to pH 2. The precipitate is recovered by filtration, washed with ethanol and Water and dried. Yield: 10 g. (42%) of 2-(l-carbethoxypentylidene)-4- thiazolidinone, melting point 138 C., light yellow needles from aqueous ethanol.

Analysis.-Calc.: C, 54.30; H, 7.04; N, 5.76; S, 13.18. Found: C, 54.24; H, 7.16; N, 5.46; S, 13.14.

EXAMPLE 15 2-(1-carbethoxypentylidene -5-methyl-4-thiazolidinone A mixture of 17 g. (0.1 mole) ethyl a-(n-butyhcyanoacetate and 12 g. (0.1 mole) methyl a-mercaptopropionate is condensed with potassium ethylate as described in Example 2. The reaction mixture is refluxed for 1% hours and is then cooled to room temperature. The precipitated potassium salt is recovered, acidified and the product purified as described in Example 2 to yield 15 g. (60%) of 2-( l-carbethoxypentylidene)-5-methyl-4-thiazolidinone, melting point 133134 C., colorless crystals from aqueous ethanol.

Analysis.Calc.: C, 56.01; H, 7.44; N, 5.44; S, 1246. Found: C, 56.12; H, 7.47; N, 5.31; S, 12.25.

EXAMPLE 16 2-(wcarbetkoxybenzylidene)-4-thiaz0iidin0ne A mixture of 18 g. (0.1 mole) ethyl phenylcyanoacetate and 12 g. (0.1 mole) ethyl mercaptoacetate is condensed with potassium ethylate as described in Example 2. The reaction mixture is maintained at 80 C. for 4 hours and is thereafter cooled to room temperature. The precipitated potassium salt is recovered, acidified and the product purified as described in Example 2 to yield 18 g. (70%) of 2-(a-carbethoxybenzylidene)-4-thiazolidinone, melting point 125 C., colorless crystals from 80% aqueous methauol or benzene/ petroleum ether.

Analysis.Calc.: C, 59.30; H, 4.98; N, 5.33; S, 12.18. Found: C, 59.22; H, 5.15; N, 5.32; S, 11.74.

EXAMPLE 17 2-(1-carbethoxy-3-diethyZaminopropylidene)-4- tii iazolidinone A mixture of 20 g. (0.1 mole) ethyl Ot-CYfillO-"Y dlfiihjllaminohutyrate and 12 g. (0.1 mole) ethyl mercaptoacetate is condensed with potassium ethy-late as described in Example 2. The reaction time is 1 hour, under reflux. The mixture is cooled to room temperature and ether is added, whereupon the potassium salt precipitates from the mixture and is recovered by filtration. The solids are treated with 50 ml. 12% aqueous HCl. Upon cooling, the pure hydrochloride salt of 2-(1 carbethoxy-3 diethylaminopropylidene)-4-thiazolidinone precipitates. Melting point 209210 C. dec., light yellow crystals from ethanol.

Analysis-Cale; C, 48.36; H, 7.18; N, 8.67; S, 9.93; C1, 10.98. Found: C, 48.40; H, 7.00; N, 8.70; S, 9.74; Cl,

EXAMPLE 18 2( 1 -carbeth0xy-3-dimethyiamirzopropylidene -4- l thiazolidilzone Equimolar quantities of ethyl ot-cyano-'y-dimethylamino- 7 butyrate and ethyl mercaptoacetate are reacted and the reaction mixture treated as described in Example 17 to yield the pure hydrochloride salt of 2-(1-carbethoxy-3- dimethylaminopropylidene) 4 thiazolidinone, melting point 229 C. dec.

Analysis.Calc.: C, 44.79; H, 6.49; N, 9.50; S, 10.87;

a Cl, 12,02. Found: C, 44.76; H, 6.53; N, 9.75; S, 10.66;

EXAMPLE 19 2-(1-carbethoxyl-diethylaminobutylidene)-4- thiazolidinone Equimolar quantities of ethyl m-cyano-w-diethylaminovalerate and ethyl mercaptoacetate are reacted and the reaction mixture treated as described in Example 17 to yield the pure hydrochloride salt of 2-(1-carbethoxy-4- diethylaminobutylidene)-4thiazolidin0ne, melting point 191-193 C. Analysis.Calc.: C, 46.67; H, 6.85; N, 9.07; S, 10.38; Cl, 11.48. Found: C, 46.54; H, 6.76; N, 8.79; S, 9.81; CI, 11.57.

EXAMPLE 20 2-(1-carbethoxy-2-phenylethylidene)-4-thiaz0lidinone A mixture of 21 g. (0.1 mole) ethyl a-cyano-fl-phenyltpropionate and 12 g. (0.1 mole) ethyl mercaptoacetate is condensed with potassium ethylate as described in Example 2. The reaction mixture is refluxed for one-half hour and is cooled. The precipitated potassium salt is acidified and the product purified as described in Example 2 to yield 2-(1-carbethoxy-2-phenylethylidene)-4-thiaz0lidinone, melting point 155l56 0, yellow needles from ethanol/dioxane 4: 1.

Analysis.-'Calc.: C, 60.63; H, 5.45; N, 5.06; S, 11.55. Found: C, 60.89; H, 5.47; N, 5.16; S, 10.91.

EXAMPLE 21 2-(1-carbeth0xy-2-phenylethylidene) --methyl-4- thiazolidinone EXAMPLE 22 2-(1,Z-dicarbethoxyethylidene)-4-thiazolidin0ne A mixture of 20 g. (0.1 mole) ethyl cyanosuccinate and 12 g. (0.1 mole ethyl mercaptoacetate is condensed with potassium ethylate as described in Example 2. The reaction conditions are 1 hour at room temperature. The precipitated pota'ssium salt is acidified and the product purified as described in Example 2 toyield 2 (1,2-dicarbethoxyethylidene)-4-thiazolidinone, melting point 98- 100 C., colorless crystals from 40% aqueous ethanol.

.Analysis.Calc.: C, 48.34; H,-5.53; N, 5.13; S, 11.73.

Found: C, 48.26; H, 5.83; N, 5.08; S, 11.71.

EXAMPLE 23 2- (1,Z-a'icarbethoxyethylidene -5-ntethyl-4- V thiazolidinone 'Equimolar quantities ofethyl cyanosuccinate and methyl ot-mercaptopropionate are reactedand the product re- .8 covered and purifiedas described in'Exa'mple 22 to yield 2 (1,2 dicarbethoxyethylidene) 5 methyl 4 thiazolidinone, melting point 102103 C.

Analysis.-Calc.: C, 50117; H, 5.97; N, 4.87; S, 11. 16. Found: C, 49.99; H, 5.94; N, 5.07; S, 11.16.

EXAMPLE 24 Z (1,3 dicarbezhoxypropylidene) 4 'thiazolidinone A mixture of 21 g. (0.1 mole) ethyl a-cyanoglutarate and 12 g. (0.1 mole) ethyl mercaptoacetate is condensed with sodium ethylate as described in Example 1. The reaction mixture is refluxed for 1 hour and then cooled. Dilution with an equal volume of Water results in the precipitation of the sodium salt which is acidified and the product purified as described in Example 1. Yield: 24 g. of 2 (1,3 dicarbethoxypropylidene) 4 thiazolidinone, melting point 122123 C., colorless crystals from benzene/petroleum ether.

Analysis.Calc.: C. 50.17; H, 5.96; N, 4.88; S, 11.16. Found: C, 50.17; H, 6.03; N, 4.96; S, 10.87.

EXAMPLE 25 2 (1,3 dicarbethoxypropylidene) 5 methyl 4 thiazolidinone Equimolar quantities of ethyl otcyanoglutarate and methyl ot-mercap-topropionate are reacted and the product recovered and purified as described in Example 24 to yield 2 (1,3 dicarbethoxyp-ropylidene) 5 methyl 4-thiazolidinone, melting point 112113 C.

Analysis.Calc.: C, 51.80; H, 6.35; N, 4.65; S. 10.64. Found: C, 52.10; H, 6.27; N, 4.81; S, 10.28.

It is understood that the foregoing detailed description is given merely by'way of illustration and that many variations may be made therein without departing from the spirit of my invention.

Having described my invention, What I desire 'to secure by Letters Patent is:

wherein R is a member selected from the group consisting of hydrogen, lower alkyl, phenyl,

R is a member selected from the group consisting of cyano,

and R is a member selected from the group consisting of hydrogen and lower alkyl.

2. 2 cyanomethylene 5 methyl 4 thiazolidinone. 3. 2 (N,N dimethylcarbamoylmethylene) 4 thiazolidinone.

- 4. 2 carbethoxymethy-lene 5 methyl -4 thiazolidinone. 5

' 5. 2 [(methylsulfonyl)methylene] 4 thiazolidinone. 6. 2 (1 carbethoxypropylidene) 4 thiazolidinone. 7. 2 (1 carbethoxypentylidene) 4 thiazolidinone. 8. 2 (1 carbethoxy 3 diethylorninapropylidene) 4 thiazolidinone. i

9. 2 (1 carbetho-xy 4 diethylaminobutylidene) 4 thiazolidinone."

10. 2 (1,2 dicarbethoxyethylidene) 4 thiazolidinone. a

1.1. 2 (1,3 dicarbethoxypropylidene) P methyl 4'- thiazolidinone.

12. A method of preparing a compound of the formula: with an a-mercapto ester of the formula wherein R is a member selected from the group consistwherein R is lower alkyl in an anhydrous reaction meing of hydrogen, lower alkyl, phenyl, dium comprising a saturated aliphatic alcohol having R is a member selected from the group consisting of 1 to 6 carbon atoms and an member selected from the wane group consisting of an alkali metal and an amine.

and R is a member selected from the group consisting of 13. A method according to claim 12 wherein the rehydrogen and g alkyl, ghlch f il f g f i action is carried out at a temperature between 25 C. and under an Oxygsn' fee amtosp 3 mm c o t 0mm the boiling point temperature of said aliphatic alcohol 30 for about one half to about eight hours.

O-CN

References (liter! by the Examiner UNITED STATES PATENTS 2,617,808 11/52 Schenck et al 260-306.7 2,865,924 12/58 Asinger et al 2-60-3061 2,957,869 10/ 6O Strube 260240 2,993,891 7/ 61 Zimmer 26()240 FOREIGN PATENTS 561,659 8/58 Canada. 641,882 8/58 Great Britain. 785,334 10/57 Great Britain.

OTHER REFERENCES Pennington et aL: J. Am. Chem. Soc., vol. 75, pp. 1091l4 (1965).

IRVING MARCUS, Primary Examiner.

WALTER A. MODANCE, Examiner. 

1. A COMPOUND OF THE FORMULA: 